Oscillatory dynamics of Rac1 activity in Dictyostelium discoideum amoebae

Area of Science:

• Cell Biology
• Biophysics
• Biochemistry

Background:

• Rho family GTPases, particularly Rac1, are crucial regulators of cell motility via actin cytoskeleton remodeling.
• In Dictyostelium discoideum, active Rac1 influences actin dynamics at the cell's leading edge and posterior cortex.

Purpose of the Study:

• To investigate the spatiotemporal dynamics of Rac1 and its effector DGAP1 in vegetative amoebae.
• To develop a theoretical model simulating these dynamics and predict novel interaction patterns.

Main Methods:

• Utilized specific fluorescent probes to monitor Rac1 and DGAP1 dynamics in live amoebae.
• Developed and employed a mass-conserving reaction-diffusion model incorporating Rac1 activation, deactivation, and DGAP1 interaction.
• Experimentally validated model predictions, including a novel colocalization regime.

Main Results:

• Observed stable polarization, rotations, and oscillations of active Rac1-enriched plasma membrane domains.
• Found DGAP1 was depleted from these active Rac1 regions, showing predominant anti-correlation.
• The reaction-diffusion model accurately reproduced experimental dynamics and predicted a new colocalization pattern.

Conclusions:

• The study enhances understanding of Rac1 GTPase behavior and its regulation in Dictyostelium.
• Demonstrates how specific interactions between Rac1 and DGAP1 lead to counterintuitive anti-correlated dynamics.
• Reveals that Rac1 dynamics and regime transitions are dependent on reaction rates, protein levels, and cell size.